JP5247442B2 - 新規アミロイド親和性化合物 - Google Patents
新規アミロイド親和性化合物 Download PDFInfo
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- JP5247442B2 JP5247442B2 JP2008522509A JP2008522509A JP5247442B2 JP 5247442 B2 JP5247442 B2 JP 5247442B2 JP 2008522509 A JP2008522509 A JP 2008522509A JP 2008522509 A JP2008522509 A JP 2008522509A JP 5247442 B2 JP5247442 B2 JP 5247442B2
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- pyridine
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- 150000001875 compounds Chemical class 0.000 title claims description 98
- 239000000203 mixture Substances 0.000 claims description 45
- 230000002285 radioactive effect Effects 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 15
- 208000024827 Alzheimer disease Diseases 0.000 claims description 13
- 238000003384 imaging method Methods 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 239000000032 diagnostic agent Substances 0.000 claims description 8
- 229940039227 diagnostic agent Drugs 0.000 claims description 8
- 238000011503 in vivo imaging Methods 0.000 claims description 5
- 231100000053 low toxicity Toxicity 0.000 claims description 5
- 230000003941 amyloidogenesis Effects 0.000 claims description 4
- 238000002603 single-photon emission computed tomography Methods 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical group OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 118
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- 239000000243 solution Substances 0.000 description 93
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- 238000006243 chemical reaction Methods 0.000 description 76
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
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- 230000002829 reductive effect Effects 0.000 description 43
- 239000000047 product Substances 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 32
- 239000002244 precipitate Substances 0.000 description 32
- 238000004128 high performance liquid chromatography Methods 0.000 description 31
- 210000004556 brain Anatomy 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 238000003786 synthesis reaction Methods 0.000 description 26
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- 239000003480 eluent Substances 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- LJYOFQHKEWTQRH-UHFFFAOYSA-N 2-bromo-1-(4-hydroxyphenyl)ethanone Chemical compound OC1=CC=C(C(=O)CBr)C=C1 LJYOFQHKEWTQRH-UHFFFAOYSA-N 0.000 description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 17
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 16
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 239000000523 sample Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 238000011156 evaluation Methods 0.000 description 14
- 239000011259 mixed solution Substances 0.000 description 14
- 239000012071 phase Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- XJKJHILCYUUVSJ-UHFFFAOYSA-N 5-methoxypyridin-2-amine Chemical compound COC1=CC=C(N)N=C1 XJKJHILCYUUVSJ-UHFFFAOYSA-N 0.000 description 11
- QJBHTNVCHGXHAB-UHFFFAOYSA-N 6-iodo-2-phenylimidazo[1,2-a]pyridine Chemical compound C=1N2C=C(I)C=CC2=NC=1C1=CC=CC=C1 QJBHTNVCHGXHAB-UHFFFAOYSA-N 0.000 description 10
- ZHWJONXIBRILIF-UHFFFAOYSA-N 4-(6-methoxyimidazo[1,2-a]pyridin-2-yl)phenol Chemical compound C=1N2C=C(OC)C=CC2=NC=1C1=CC=C(O)C=C1 ZHWJONXIBRILIF-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000004364 calculation method Methods 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- YBOCOHMLQZAQQZ-UHFFFAOYSA-N 4-(6-iodoimidazo[1,2-a]pyridin-2-yl)phenol Chemical compound C1=CC(O)=CC=C1C1=CN(C=C(I)C=C2)C2=N1 YBOCOHMLQZAQQZ-UHFFFAOYSA-N 0.000 description 8
- 208000037259 Amyloid Plaque Diseases 0.000 description 8
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000009825 accumulation Methods 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 230000007886 mutagenicity Effects 0.000 description 8
- 231100000299 mutagenicity Toxicity 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- ZKEAOLVGPKCNCT-UHFFFAOYSA-N 2-bromo-3-methoxy-6-nitropyridine Chemical compound COC1=CC=C([N+]([O-])=O)N=C1Br ZKEAOLVGPKCNCT-UHFFFAOYSA-N 0.000 description 7
- PDOWLYNSFYZIQX-UHFFFAOYSA-N 2-bromo-3-methoxypyridine Chemical compound COC1=CC=CN=C1Br PDOWLYNSFYZIQX-UHFFFAOYSA-N 0.000 description 7
- 230000008499 blood brain barrier function Effects 0.000 description 7
- KPMVHELZNRNSMN-UHFFFAOYSA-N chembl1985849 Chemical compound N1=CC=C2NCCN21 KPMVHELZNRNSMN-UHFFFAOYSA-N 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- KRHYYFGTRYWZRS-BJUDXGSMSA-M fluorine-18(1-) Chemical compound [18F-] KRHYYFGTRYWZRS-BJUDXGSMSA-M 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- 239000012488 sample solution Substances 0.000 description 7
- JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- HQVATKNWZYCFHS-UHFFFAOYSA-N 3-[4-(6-methoxyimidazo[1,2-a]pyridin-2-yl)phenoxy]propyl 4-methylbenzenesulfonate Chemical compound C=1N2C=C(OC)C=CC2=NC=1C(C=C1)=CC=C1OCCCOS(=O)(=O)C1=CC=C(C)C=C1 HQVATKNWZYCFHS-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- VNHWPVLQRKKKRY-UHFFFAOYSA-N 1-bromo-3-fluoropropane Chemical compound FCCCBr VNHWPVLQRKKKRY-UHFFFAOYSA-N 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 0 CC(C)(C*)CC(C)(C)COCc(cc1)ccc1-c1c[n](C=IC=C2)c2n1 Chemical compound CC(C)(C*)CC(C)(C)COCc(cc1)ccc1-c1c[n](C=IC=C2)c2n1 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 229940125782 compound 2 Drugs 0.000 description 5
- 229940126214 compound 3 Drugs 0.000 description 5
- 238000009206 nuclear medicine Methods 0.000 description 5
- 239000003444 phase transfer catalyst Substances 0.000 description 5
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- BCQLNMVTXCZBFR-UHFFFAOYSA-N 2-[4-(3-fluoropropoxy)phenyl]imidazo[1,2-a]pyridine Chemical compound C1=CC(OCCCF)=CC=C1C1=CN(C=CC=C2)C2=N1 BCQLNMVTXCZBFR-UHFFFAOYSA-N 0.000 description 4
- YKHQFTANTNMYPP-UHFFFAOYSA-N 2-bromopyridin-3-ol Chemical compound OC1=CC=CN=C1Br YKHQFTANTNMYPP-UHFFFAOYSA-N 0.000 description 4
- DJAPVDCXTHRTAM-UHFFFAOYSA-N 4-(6-bromoimidazo[1,2-a]pyridin-2-yl)phenol Chemical compound C1=CC(O)=CC=C1C1=CN(C=C(Br)C=C2)C2=N1 DJAPVDCXTHRTAM-UHFFFAOYSA-N 0.000 description 4
- ZWIARAQZLULYPG-NSCUHMNNSA-N 4-[(e)-2-[4-(methylamino)phenyl]ethenyl]phenol Chemical compound C1=CC(NC)=CC=C1\C=C\C1=CC=C(O)C=C1 ZWIARAQZLULYPG-NSCUHMNNSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 4
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- -1 [18 F] fluoride ions Chemical class 0.000 description 4
- 206010002022 amyloidosis Diseases 0.000 description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 238000005192 partition Methods 0.000 description 4
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- 239000002243 precursor Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- IAVCEBMLYVGBLA-UHFFFAOYSA-N 2-[1-[6-[2-fluoroethyl(methyl)amino]naphthalen-2-yl]ethylidene]propanedinitrile Chemical compound C1=C(C(C)=C(C#N)C#N)C=CC2=CC(N(CCF)C)=CC=C21 IAVCEBMLYVGBLA-UHFFFAOYSA-N 0.000 description 3
- YDMVHZJFEJLHGF-SQZVAGKESA-N 2-[4-(3-fluoranylpropoxy)phenyl]-6-methoxyimidazo[1,2-a]pyridine Chemical compound C=1N2C=C(OC)C=CC2=NC=1C1=CC=C(OCCC[18F])C=C1 YDMVHZJFEJLHGF-SQZVAGKESA-N 0.000 description 3
- VXUPSLFKOTYIPR-UHFFFAOYSA-N 2-[4-(3-fluoropropoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine Chemical compound C1=CC(OCCCF)=CC=C1C1=CN(C=C(I)C=C2)C2=N1 VXUPSLFKOTYIPR-UHFFFAOYSA-N 0.000 description 3
- YDMVHZJFEJLHGF-UHFFFAOYSA-N 2-[4-(3-fluoropropoxy)phenyl]-6-methoxyimidazo[1,2-a]pyridine Chemical compound C=1N2C=C(OC)C=CC2=NC=1C1=CC=C(OCCCF)C=C1 YDMVHZJFEJLHGF-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000003920 cognitive function Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
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- 238000004519 manufacturing process Methods 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
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- 239000008363 phosphate buffer Substances 0.000 description 3
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- 238000012636 positron electron tomography Methods 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 3
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000005185 salting out Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- DKFFAVRVYDPJBA-UHFFFAOYSA-N tributyl-[2-[4-(3-fluoropropoxy)phenyl]imidazo[1,2-a]pyridin-6-yl]stannane Chemical compound C=1N2C=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=1C1=CC=C(OCCCF)C=C1 DKFFAVRVYDPJBA-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- LLEVBSPEOUODSV-UHFFFAOYSA-N 2-(4-hydroxyphenyl)imidazo[1,2-a]pyridin-6-ol Chemical compound C1=CC(O)=CC=C1C1=CN(C=C(O)C=C2)C2=N1 LLEVBSPEOUODSV-UHFFFAOYSA-N 0.000 description 2
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| JP2006188034 | 2006-07-07 | ||
| PCT/JP2007/062503 WO2007148755A1 (ja) | 2006-06-21 | 2007-06-21 | 新規アミロイド親和性化合物 |
| JP2008522509A JP5247442B2 (ja) | 2006-06-21 | 2007-06-21 | 新規アミロイド親和性化合物 |
Publications (2)
| Publication Number | Publication Date |
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| JPWO2007148755A1 JPWO2007148755A1 (ja) | 2009-11-19 |
| JP5247442B2 true JP5247442B2 (ja) | 2013-07-24 |
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| JP2008522509A Active JP5247442B2 (ja) | 2006-06-21 | 2007-06-21 | 新規アミロイド親和性化合物 |
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| Country | Link |
|---|---|
| JP (1) | JP5247442B2 (zh) |
| ES (1) | ES2629768T3 (zh) |
| NZ (1) | NZ574164A (zh) |
| TW (1) | TW200811175A (zh) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6391391A (ja) * | 1986-09-22 | 1988-04-22 | オーソ・フアーマシユーチカル・コーポレーシヨン | ２−または３−アリール置換イミダゾ［１，２−ａ］ビリジン |
| JP2001503048A (ja) * | 1996-10-30 | 2001-03-06 | リヒター ゲデオン ベジェセティ ジャール アールテー． | ２―メトキシフェニルピペラジン誘導体 |
| WO2001074815A2 (en) * | 2000-03-31 | 2001-10-11 | Ortho Mcneil Pharmaceutical, Inc. | Phenyl-substituted imidazopyridines |
| WO2001074813A2 (en) * | 2000-03-31 | 2001-10-11 | Ortho Mcneil Pharmaceutical, Inc. | METHOD FOR USING 2- OR 3-ARYL SUBSTITUTED IMIDAZO[1,2-a] PYRIDINES AS H3 ANTAGONISTS |
| JP2004506633A (ja) * | 2000-08-16 | 2004-03-04 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | 新規β−アミロイド阻害剤、その製造方法及び医薬組成物としての使用 |
| JP2005526749A (ja) * | 2002-03-06 | 2005-09-08 | ノバルティス アクチエンゲゼルシャフト | バイオマーカーとして有用なクマリン |
| WO2007135890A1 (ja) * | 2006-05-19 | 2007-11-29 | Nihon Medi-Physics Co., Ltd. | 新規アミロイド親和性化合物 |
-
2007
- 2007-06-20 TW TW96122176A patent/TW200811175A/zh unknown
- 2007-06-21 NZ NZ574164A patent/NZ574164A/en not_active IP Right Cessation
- 2007-06-21 ES ES07767329.1T patent/ES2629768T3/es active Active
- 2007-06-21 JP JP2008522509A patent/JP5247442B2/ja active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6391391A (ja) * | 1986-09-22 | 1988-04-22 | オーソ・フアーマシユーチカル・コーポレーシヨン | ２−または３−アリール置換イミダゾ［１，２−ａ］ビリジン |
| JP2001503048A (ja) * | 1996-10-30 | 2001-03-06 | リヒター ゲデオン ベジェセティ ジャール アールテー． | ２―メトキシフェニルピペラジン誘導体 |
| WO2001074815A2 (en) * | 2000-03-31 | 2001-10-11 | Ortho Mcneil Pharmaceutical, Inc. | Phenyl-substituted imidazopyridines |
| WO2001074813A2 (en) * | 2000-03-31 | 2001-10-11 | Ortho Mcneil Pharmaceutical, Inc. | METHOD FOR USING 2- OR 3-ARYL SUBSTITUTED IMIDAZO[1,2-a] PYRIDINES AS H3 ANTAGONISTS |
| JP2004506633A (ja) * | 2000-08-16 | 2004-03-04 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | 新規β−アミロイド阻害剤、その製造方法及び医薬組成物としての使用 |
| JP2005526749A (ja) * | 2002-03-06 | 2005-09-08 | ノバルティス アクチエンゲゼルシャフト | バイオマーカーとして有用なクマリン |
| WO2007135890A1 (ja) * | 2006-05-19 | 2007-11-29 | Nihon Medi-Physics Co., Ltd. | 新規アミロイド親和性化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2629768T3 (es) | 2017-08-14 |
| TW200811175A (en) | 2008-03-01 |
| NZ574164A (en) | 2012-01-12 |
| JPWO2007148755A1 (ja) | 2009-11-19 |
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